On Cancer: Memorial Sloan Kettering Featured Prominently at Major Cancer Research Meeting

Two Memorial Sloan Kettering studies about targeted cancer therapies received recognition in the press program for one of the nation’s premier cancer research events: the American Association for Cancer Research (AACR) Annual Meeting 2014, held April 5–9 in San Diego. The press program highlights cancer research that a panel of AACR experts considers the most significant of the year and deserving of media attention.

In addition, several Memorial Sloan Kettering investigators received awards and assumed leadership roles.

The AACR meeting brings together roughly 18,000 researchers, patient advocates, and other professionals in the cancer field to present the latest basic, translational, and clinical discoveries. Memorial Sloan Kettering cancer biologist Scott Lowe, who chairs the Geoffrey Beene Cancer Research Center, served as the meeting’s Scientific Program Committee Chairperson.

IDH2 normally makes a protein that plays a critical role in cellmetabolism. However, when the gene is mutated, it can lead to the production of an abnormal protein that is thought to cause some types of cancer — including AML and MDS — by preventing healthy bone marrow cells from maturing.

Dr. Stein presented preliminary results on ten patients who received one of two doses of AG-221 twice daily. Three patients were not able to complete a full cycle of therapy due to complications of their disease, but six of the remaining seven patients had responses, including three complete remissions.

While phase I clinical trials are designed primarily to determine the safety and tolerability of a new drug, Dr. Stein said he is encouraged by the results he’s seen thus far with AG-221 and its implications for the emerging field of targeting cancer metabolism.

Identifying Mechanism by Which Tumors Become Resistant

BYL719 is an investigational drug that targets PI3K-alpha, a gene known to be mutated in a third of breast cancers and to play an important role in the disease. Castel and his colleagues sequenced the DNA of multiple metastatic tumors from a patient who initially responded dramatically to BYL719 but whose cancer eventually returned. Some of these metastatic tumors were sensitive to BYL719 while others proved resistant.

By comparing the DNA of the two tumor types, the researchers found that the resistant tumors had different mutations in the gene PTEN that may have caused the drug to stop working. The responsive tumors contained normally functioning PTEN genes.

Using mouse models, the researchers were able to show that combining BYL719 with a drug that targets another protein responsible for the resistance “reeducated” the cancer to respond to treatment. Castel said that the results stress the importance of developing dynamic therapy so that physicians can adjust treatment as tumors evolve and acquire new mutations that cause drug resistance.

Awards and Appointments for Memorial Sloan Kettering Staff

Several Memorial Sloan Kettering investigators were honored at the meeting.

Maurizio Scaltriti, an Assistant Lab Member in the Human Oncology and Pathogenesis Program (HOPP), was named one of the AACR's “NextGen Stars.” For the first time, the AACR accepted applications from early-career investigators to present their research during selected major symposia. Dr. Scaltriti was chosen as one of five investigators from more than 100 applicants.

Dr. Stein’s research was funded by Agios Pharmaceuticals; Pau Castel’s research was funded by Stand Up To Cancer and the Breast Cancer Research Foundation.

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abnormal (ab-NOR-mul)

Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

acute (uh-KYOOT)

Symptoms or signs that begin and worsen quickly; not chronic.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

AML

An aggressive (fast-growing) disease in which too many myeloblasts (immature white blood cells that are not lymphoblasts) are found in the bone marrow and blood. Also called acute myeloblastic leukemia, acute myelogenous leukemia, acute myeloid leukemia, acute nonlymphocytic leukemia, and ANLL.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

blood (blud)

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

bone marrow (bone MAYR-oh)

The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cancer (KAN-ser)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cell (sel)

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

clinical (KLIH-nih-kul)

Having to do with the examination and treatment of patients.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

clinical trial (KLIH-nih-kul TRY-ul)

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

DNA

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

drug (drug)

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

drug resistance (... reh-ZIH-stunts)

The failure of cancer cells, viruses, or bacteria to respond to a drug used to kill or weaken them. The cells, viruses, or bacteria may be resistant to the drug at the beginning of treatment, or may become resistant after being exposed to the drug.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

gene (jeen)

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

immunotherapy (IH-myoo-noh-THAYR-uh-pee)

Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in immunotherapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called biological response modifier therapy, biological therapy, biotherapy, and BRM therapy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

investigational (in-VES-tih-GAY-shuh-nul)

In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered investigational in other diseases or conditions. Also called experimental.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

investigator (in-VES-tih-gay-ter)

A researcher in a clinical trial or clinical study.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

leukemia (loo-KEE-mee-uh)

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

medical oncologist (MEH-dih-kul on-KAH-loh-jist)

A doctor who specializes in diagnosing and treating cancer using chemotherapy, hormonal therapy, biological therapy, and targeted therapy. A medical oncologist often is the main health care provider for someone who has cancer. A medical oncologist also gives supportive care and may coordinate treatment given by other specialists.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

melanoma (MEH-luh-NOH-muh)

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

metabolism (meh-TA-buh-lih-zum)

The chemical changes that take place in a cell or an organism. These changes make energy and the materials cells and organisms need to grow, reproduce, and stay healthy. Metabolism also helps get rid of toxic substances.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

metastatic (meh-tuh-STA-tik)

Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

myeloid (MY-eh-loyd)

Having to do with or resembling the bone marrow. May also refer to certain types of hematopoietic (blood-forming) cells found in the bone marrow. Sometimes used as a synonym for myelogenous; for example, acute myeloid leukemia and acute myelogenous leukemia are the same disease.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

oncology (on-KAH-loh-jee)

The study of cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

pancreatic (PAN-kree-A-tik)

Having to do with the pancreas.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

protein (PROH-teen)

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

resistance

Failure of a cancer to shrink after treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

significant (sig-NIH-fih-kunt)

In statistics, describes a mathematical measure of difference between groups. The difference is said to be significant if it is greater than what might be expected to happen by chance alone. Also called statistically significant.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

stress (stres)

The response of the body to physical, mental, or emotional pressure. This may make a person feel frustrated, angry, or anxious, and may cause unhealthy chemical changes in the body. Untreated, long-term stress may lead to many types of mental and physical health problems.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

therapy (THAYR-uh-pee)

Treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

tumor (TOO-mer)

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

will (wil)

A legal document in which a person states what is to be done with his or her property after death, who is to carry out the terms of the will, and who is to care for any minor children.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)